Arthropod-borne bacteria must cope with the immune systems of both a vertebrate host and an invertebrate vector. Recently it has been discovered that arthropods are able to mount effective inducible immune responses and these responses are beginning to be characterized in model insects such as Drosophila and tobacco hornworm. We plan to follow the work published on these models to characterize the immune response of medically important arthropods that transmit bacterial pathogens, namely fleas and ticks. For example, after Borrelia spirochetes enter the tick?s gut in a blood meal, the spirochetes must penetrate the gut wall and migrate through the tick body cavity to the salivary glands in preparation for transmission to a new mammalian host. During this process they would be expected to be exposed to the tick?s immune response. How the spirochetes avoid it is unknown. Once the normal antibacterial immune response of the tick is characterized, we plan to study the mechanisms by which Borrelia spirochetes are able to overcome them. These studies may be central to understanding infection of the tick vector as analogous studies of the mammalian immune system have been to understanding infection of the mammal. These investigations may also shed light on the the strict association of certain Borrelia species with certain ticks, i.e., whether the tick immune response is involved in determining vector competence.